title: Nanoparticles inhibit DNA replication by binding to DNA: modeling and experimental validation.
abstract: Predictive models are beneficial tools for researchers to use in prioritizing nanoparticles (NPs) for toxicological tests, but experimental evaluation can be time-consuming and expensive, and thus, priority should be given to tests that identify the NPs most likely to be harmful. For characterization of NPs, the physical binding of NPs to DNA molecules is important to measure, as interference with DNA function may be one cause of toxicity. Here, we determined the interaction energy between 12 types of NPs and DNA based on the Derjaguin-Landau-Verwey-Overbeek (DLVO) model and then predicted the affinity of the NPs for DNA. Using the single-molecule imaging technique known as atomic force microscopy (AFM), we experimentally determined the binding affinity of those NPs for DNA. Theoretical predictions and experimental observations of the binding affinity agreed well. Furthermore, the effect of NPs on DNA replication in vitro was investigated with the polymerase chain reaction (PCR) technique. The results showed that NPs with a high affinity for DNA strongly inhibited DNA replication, whereas NPs with low affinity had no or minimal effects on DNA replication. The methodology here is expected to benefit the genotoxicological testing of NPs as well as the design of safe NPs.
authors.affiliation: School of Civil and Environmental Engineering, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Kungang
authors.initials: K
authors.lastname: Li
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhao
authors.forename: Brian
authors.initials: B
authors.lastname: K Hammer
authors.forename: Songyan
authors.initials: S
authors.lastname: Du
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chen
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004269:DNA, Bacterial / Q000187:drug effects; D006657:Histones / Q000737:chemistry; D006801:Humans; D018625:Microscopy, Atomic Force; D015233:Models, Statistical; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D016133:Polymerase Chain Reaction; D045663:Quantum Dots
chemical_list: D004269:DNA, Bacterial; D006657:Histones; D004247:DNA